1. Field of the Invention
The present invention relates to a polypeptide having an activity to support proliferation or survival of hematopoietic stem cells or hematopoietic progenitor cells, a DNA coding the polypeptide, and a pharmaceutical composition comprising the polypeptide as active ingredient.
2. Description of the Related Art
Fully differentiated mature hematopoietic cells have limited short lives. Homeostasis of the blood is maintained due to supply of the mature blood cells caused by continuous differentiation of hematopoietic progenitor cells. The hematopoietic progenitor cells are giving rise from more undifferentiated hematopoietic stem cells. The hematopoietic stem cells have potential of differentiating into all of the differentiation lineages (totipotency) and have potential of self-renew with retaining the totipotency so as to supply the hematopoietic cells through life. That is, the hematopoietic stem cells are known to generate totipotent stem cells by the self-renew and to differentiate in parts to a variety of the mature blood cells through the hematopoietic progenitor cells.
This differentiation of the blood cells is regulated by a variety of cytokines. Erythropoietin is known to promote the differentiation of the erythrocytic lineages. G-CSF and thrombopoietin are also known to promote the differentiation of the neutrophils, and the megakaryocytes and the platelet productive cells, respectively. However, a factor required for the self-renew of the hematopoietic stem cell with retaining the totipotency has not been clear. Although SCF/MGF (Williams, D. E., Cell, 63: 167-174, 1990; Zsebo, K. M., Cell, 63: 213-224, 1990), SCGF (WO98/08869), and the like are reported as growth factors for the hematopoietic stem cells, none of them have potency to sufficiently retain the totipotency of the hematopoietic stem cells. Although attempts to culture the hematopoietic stem cells in the presence of combinations of known cytokines, a system for efficient amplification of the hematopoietic stem cells was not realized (Miller, C. L., Proc. Natl. Acad. Sci. USA, 94: 13648-13653, 1997; Yagi, M., Proc. Natl. Acad. Sci. USA, 96: 8126-8131, 1999; Shih, C. C., Blood, 94: 5 1623-1636, 1999).
On the other hand, attempts to allow the hematopoietic stem cells to survive or proliferate without differentiation by using stromal cells which supply an environment suitable for survival or proliferation of the hematopoietic stem cells were reported (Moore K. A., Blood, 89: 12, 4337-4347, 1997). In addition, WO99/03980 discloses a stromal cell line capable of supporting proliferation or survival of hematopoietic stem cells and hematopoietic progenitor cells, which are established from an AGM (Aorta-Gonad-Mesonephros) region of a fetal mouse.
It is postulated that there should be more peptides that efficiently facilitate hematopoietic stem cell and progenitor cell amplification by themselves or in combination with stromal cells or stimulating factors such as cytokines, in addition to known factors affecting hematopoietic cells.